This multidisciplinary research program employs innovative analytical chemical and neurophysiological methods for studying interrelated clinical, pharmacological, and neurophysiological aspects of epilepsy. Analysis of temporal variability and biorhythms figures prominently in the experimental design. Analytical chemical methods include atmospheric ionization, mass spectrometry, and gas liquid chromatography, with real-time process control by dedicated laboratory computers. OBJECTIVES: (1) to develop rapid, highly specific methods for assay of anticonvulsants; (2) to determine the biochemical mechanisms of toxicity of anticonvulsant drugs; and (3) to develop economical quantitative and entirely objective techniques for defining the characteristics of EEG signals, especially those relevant to the investigation of epileptic patients. The neurophysiological methods include computer-assisted visual EEG analysis and automatic quantification of background and paroxysmal EEG activity. The pharmacological studies and the studies of patterns of clinical and electrical epileptic activity over time examine therapeutic response in a parametric design (using previously untreated patients) as a function of serum drug levels, clinical seizure incidence, EEG seizure discharges, background EEG changes, evoked potentials, and manifestations of toxicity. Background and paroxysmal EEG activity are studied by continuous recording for 36-48 hours before and after institution of anticonvulsant therapy. Electrophysiological features will be described by statistical analysis of resulting time series, with special attention to treatment response and influence of diurnal, nocturnal, and ultradian rhythms as they relate to hazard-determined dose scheduling and outcome of therapy. Neurophysiological methods of seizure control involving mobilization of physiological inhibitory brain mechanisms are investigated, using chronic primate and other animal models.